The genetic basis for adaptation of model-designed syntrophic co-cultures.

Understanding the fundamental characteristics of microbial communities could have far reaching implications for human health and applied biotechnology. Despite this, much is still unknown regarding the genetic basis and evolutionary strategies underlying the formation of viable synthetic communities. By pairing auxotrophic mutants in co-culture, it has been demonstrated that viable nascent E. coli communities can be established where the mutant strains are metabolically coupled. A novel algorithm, OptAux, was constructed to design 61 unique multi-knockout E. coli auxotrophic strains that require significant metabolite uptake to grow. These predicted knockouts included a diverse set of novel non-specific auxotrophs that result from inhibition of major biosynthetic subsystems. Three OptAux predicted non-specific auxotrophic strains-with diverse metabolic deficiencies-were co-cultured with an L-histidine auxotroph and optimized via adaptive laboratory evolution (ALE). Time-course sequencing revealed the genetic changes employed by each strain to achieve higher community growth rates and provided insight into mechanisms for adapting to the syntrophic niche. A community model of metabolism and gene expression was utilized to predict the relative community composition and fundamental characteristics of the evolved communities. This work presents new insight into the genetic strategies underlying viable nascent community formation and a cutting-edge computational method to elucidate metabolic changes that empower the creation of cooperative communities

Low-frequency radio observations of recurrent nova RS Ophiuchi with MeerKAT and LOFAR

We report low-frequency radio observations of the 2021 outburst of the recurrent nova RS Ophiuchi. These observations include the lowest frequency observations of this system to date. Detailed light curves are obtained by MeerKAT at 0.82 and 1.28 GHz and LOFAR at 54 and 154 MHz. These low-frequency detections allow us to put stringent constraints on the brightness temperature that clearly favour a non-thermal emission mechanism. The radio emission is interpreted and modelled as synchrotron emission from the shock interaction between the nova ejecta and the circumbinary medium. The light curve shows a plateauing behaviour after the first peak, which can be explained by either a non-uniform density of the circumbinary medium or a second emission component. Allowing for a second component in the light curve modelling captures the steep decay at late times. Furthermore, extrapolating this model to 15 years after the outburst shows that the radio emission might not fully disappear between outbursts. Further modelling of the light curves indicates a red giant mass loss rate of $\sim 5 \cdot 10^{-8}~{\rm M_\odot~yr^{-1}}$. The spectrum cannot be modelled in detail at this stage, as there are likely at least four emission components. Radio emission from stellar wind or synchrotron jets are ruled out as the possible origin of the radio emission. Finally, we suggest a strategy for future observations that would advance our understanding of the physical properties of RS Oph.Comment: submitted to MNRA

Nitrate removal in stream ecosystems measured by 15N addition experiments: Total uptake

We measured uptake length of 15NO3− in 72 streams in eight regions across the United States and Puerto Rico to develop quantitative predictive models on controls of NO3− uptake length. As part of the Lotic Intersite Nitrogen eXperiment II project, we chose nine streams in each region corresponding to natural (reference), suburban-urban, and agricultural land uses. Study streams spanned a range of human land use to maximize variation in NO3− concentration, geomorphology, and metabolism. We tested a causal model predicting controls on NO3− uptake length using structural equation modeling. The model included concomitant measurements of ecosystem metabolism, hydraulic parameters, and nitrogen concentration. We compared this structural equation model to multiple regression models which included additional biotic, catchment, and riparian variables. The structural equation model explained 79% of the variation in log uptake length (SWtot). Uptake length increased with specific discharge (Q/w) and increasing NO3− concentrations, showing a loss in removal efficiency in streams with high NO3− concentration. Uptake lengths shortened with increasing gross primary production, suggesting autotrophic assimilation dominated NO3− removal. The fraction of catchment area as agriculture and suburban-urban land use weakly predicted NO3− uptake in bivariate regression, and did improve prediction in a set of multiple regression models. Adding land use to the structural equation model showed that land use indirectly affected NO3− uptake lengths via directly increasing both gross primary production and NO3− concentration. Gross primary production shortened SWtot, while increasing NO3− lengthened SWtot resulting in no net effect of land use on NO3− removal

Nitrate removal in stream ecosystems measured by 15N addition experiments: Denitrification

We measured denitrification rates using a field 15NO3− tracer-addition approach in a large, cross-site study of nitrate uptake in reference, agricultural, and suburban-urban streams. We measured denitrification rates in 49 of 72 streams studied. Uptake length due to denitrification (SWdenn) ranged from 89 m to 184 km (median of 9050 m) and there were no significant differences among regions or land-use categories, likely because of the wide range of conditions within each region and land use. N2 production rates far exceeded N2O production rates in all streams. The fraction of total NO3− removal from water due to denitrification ranged from 0.5% to 100% among streams (median of 16%), and was related to NH4+ concentration and ecosystem respiration rate (ER). Multivariate approaches showed that the most important factors controlling SWden were specific discharge (discharge / width) and NO3− concentration (positive effects), and ER and transient storage zones (negative effects). The relationship between areal denitrification rate (Uden) and NO3− concentration indicated a partial saturation effect. A power function with an exponent of 0.5 described this relationship better than a Michaelis-Menten equation. Although Uden increased with increasing NO3− concentration, the efficiency of NO3− removal from water via denitrification declined, resulting in a smaller proportion of streamwater NO3− load removed over a given length of stream. Regional differences in stream denitrification rates were small relative to the proximate factors of NO3− concentration and ecosystem respiration rate, and land use was an important but indirect control on denitrification in streams, primarily via its effect on NO3− concentration

Steel Deck Diaphragm Test Database V1.0

Front material and Excel database of test results.From the 1950’s to the present, a substantial number of large-scale tests have been conducted on steel deck diaphragms or concrete on metal deck diaphragms. The data, papers and reports for these tests are located in scattered references and many are not publically available. As part of the Steel Diaphragm Innovation Initiative (SDII), a database of over 750 past experiments on metal deck diaphragms was created. The information contained in this database can be useful for several applications including evaluating strength and stiffness prediction equations, assessing resistance and safety factors, and investigating ductility of diaphragms. The database contains fields related to 1) specimen identification and reference, 2) the test setup including information about the geometry, loading type, deck orientation, beam sizes, steel deck geometry, and concrete slab information if applicable, 3) fastener information including sidelap fasteners, structural fasteners, and shear studs, 4) information about materials including deck material and concrete fill material, and 5) test results for selected specimens including stiffness, strength, and ductility.American Institute of Steel Construction (AISC), American Iron and Steel Institute (AISI), Steel Deck Institute (SDI), Steel Joist Institute (SJI), Metal Building Manufacturers Association (MBMA), National Science Foundation (NSF

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

The Ensemble Photometric Variability of ~25000 Quasars in the Sloan Digital Sky Survey

Using a sample of over 25000 spectroscopically confirmed quasars from the Sloan Digital Sky Survey, we show how quasar variability in the rest frame optical/UV regime depends upon rest frame time lag, luminosity, rest wavelength, redshift, the presence of radio and X-ray emission, and the presence of broad absorption line systems. The time dependence of variability (the structure function) is well-fit by a single power law on timescales from days to years. There is an anti-correlation of variability amplitude with rest wavelength, and quasars are systematically bluer when brighter at all redshifts. There is a strong anti-correlation of variability with quasar luminosity. There is also a significant positive correlation of variability amplitude with redshift, indicating evolution of the quasar population or the variability mechanism. We parameterize all of these relationships. Quasars with RASS X-ray detections are significantly more variable (at optical/UV wavelengths) than those without, and radio loud quasars are marginally more variable than their radio weak counterparts. We find no significant difference in the variability of quasars with and without broad absorption line troughs. Models involving multiple discrete events or gravitational microlensing are unlikely by themselves to account for the data. So-called accretion disk instability models are promising, but more quantitative predictions are needed.Comment: 41 pages, 21 figures, AASTeX, Accepted for publication in Ap

Quantum Optical Metrology of Correlated Phase and Loss

Optical absorption measurements characterize a wide variety of systems from atomic gases to in vivo diagnostics of living organisms. Here we study the potential of nonclassical techniques to reduce statistical noise below the shot-noise limit in absorption measurements with concomitant phase shifts imparted by a sample. We consider both cases where there is a known relationship between absorption and a phase shift, and where this relationship is unknown. For each case we derive the fundamental limit and provide a practical strategy to reduce statistical noise. Furthermore, we find an intuitive correspondence between measurements of absorption and of lossy phase shifts, which both show the same analytical form for precision enhancement for bright states. Our results demonstrate that nonclassical techniques can aid real-world tasks with present-day laboratory techniques